U.S. patent number 10,500,382 [Application Number 15/808,610] was granted by the patent office on 2019-12-10 for drug-filled stents with filaments for increased lumen surface area and method of manufacture thereof.
This patent grant is currently assigned to Medtronic Vascular, Inc.. The grantee listed for this patent is Medtronic Vascular, Inc.. Invention is credited to Ryan Bienvenu, Michael Harms, Justin Peterson, Stefan Tunev.
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United States Patent |
10,500,382 |
Bienvenu , et al. |
December 10, 2019 |
Drug-filled stents with filaments for increased lumen surface area
and method of manufacture thereof
Abstract
A stent including a hollow wire formed into a stent pattern. The
hollow wire includes an outer member having an outer surface and an
inner surface, a lumen extending longitudinally within the hollow
wire, at least one opening extending from the outer surface of the
outer member to the lumen, and a plurality of filaments extending
longitudinally within the lumen. The plurality of filaments
increases the amount of surface area available for tissue in-growth
within the lumen. Each filament of the plurality of filaments is
spaced from adjacent filaments of the plurality of filaments, and
the spacing between adjacent filaments of the plurality of
filaments is configured to permit tissue in-growth between the
adjacent filaments.
Inventors: |
Bienvenu; Ryan (Santa Rosa,
CA), Peterson; Justin (Santa Rosa, CA), Tunev; Stefan
(Santa Rosa, CA), Harms; Michael (Santa Rosa, CA) |
Applicant: |
Name |
City |
State |
Country |
Type |
Medtronic Vascular, Inc. |
Santa Rosa |
CA |
US |
|
|
Assignee: |
Medtronic Vascular, Inc. (Santa
Rosa, CA)
|
Family
ID: |
60484483 |
Appl.
No.: |
15/808,610 |
Filed: |
November 9, 2017 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20180126135 A1 |
May 10, 2018 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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62420473 |
Nov 10, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F
2/86 (20130101); A61L 31/16 (20130101); A61M
31/002 (20130101); A61F 2/88 (20130101); A61L
31/022 (20130101); A61L 31/18 (20130101); A61F
2250/0068 (20130101); A61F 2250/0051 (20130101); A61F
2230/0013 (20130101); A61F 2002/91575 (20130101); A61F
2002/91541 (20130101); A61F 2230/0006 (20130101); A61F
2240/001 (20130101); A61F 2250/0098 (20130101) |
Current International
Class: |
A61F
2/88 (20060101); A61M 31/00 (20060101); A61F
2/86 (20130101); A61L 31/02 (20060101); A61L
31/18 (20060101); A61L 31/16 (20060101); A61F
2/915 (20130101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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2008/063780 |
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May 2008 |
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WO |
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2008/106223 |
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Sep 2008 |
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WO |
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2014/162902 |
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Oct 2014 |
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WO |
|
Other References
Lee, Jung-Jin et al., "Evaluation of Effect of Galvanic Corrosion
Between Nickel-Chromium Metal and Titanium on Ion Release and Cell
Toxicity" J Adv Prosthodont 2015;7:172-7, pp. 1-6. cited by
applicant .
Devine, D.M. et al., "Tissue Reaction to Implants of Different
Metals: A Study Using Guide Wires in Cannulated Screws"
www.ecmjournal.org, European Cells and Materials, vol. 18 2009 (pp.
40-48), pp. 40-48. cited by applicant .
Sansone, Valerio et al., "The Effects on Bone Cells of Metal Ions
Released From Orthopaedic Implants. A Review" Clinical Cases in
Mineral and Bone Metabolism 2013; 10(1): 34-40. cited by applicant
.
Acevedo, Daniel, MD et al., "Mixing Implants of Differing Metallic
Composition in the Treatment of Upper-Extremity Fractures"
www.healio.com/orthopedics/journals/ortho, Orthopedics, Sep. 2013,
vol. 36, Issue 9, e1175-e1179. cited by applicant .
Cwikiel W et al, "Electrolytic Stents to Inhibit Tumor Growth. An
experimental study in vitro and in rats," Acta Radiologica, Informa
Healthcare, GB, vol. 34, No. 3, May 1, 1993 (May 1, 1993), pp.
258-262. cited by applicant .
International Search Report and the Written Opinion of the
International Searching Authority issued in PCT/US2017/060947,
dated Jan. 31, 2018. cited by applicant.
|
Primary Examiner: Ganesan; Suba
Attorney, Agent or Firm: Medler Ferro Woodhouse & Mills
PLLC
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit under 35 U.S.C. .sctn. 119(e)
of the filing date of U.S. Provisional Application No. 62/420,473
filed Nov. 10, 2016, the contents of which are incorporated by
reference herein, in their entirety.
Claims
What is claimed is:
1. A stent comprising: a hollow wire formed into a stent pattern,
wherein the hollow wire includes: an outer member having an outer
surface and an inner surface; an intermediate member lining at
least a portion of the inner surface of the outer member, the
intermediate member having an outer surface and an inner surface; a
lumen extending longitudinally within the hollow wire, wherein the
lumen is defined by the inner surface of the intermediate member
and extends longitudinally within the intermediate member; at least
one opening disposed through the outer member to the lumen, wherein
the at least one opening is disposed through the outer member and
the intermediate member to the lumen; and at least one filament
extending longitudinally within the lumen, wherein the at least one
filament increases the amount of surface area available for tissue
in-growth within the lumen.
2. The stent of claim 1, wherein the at least one filament extends
a full length of the hollow wire.
3. The stent of claim 1, wherein the at least one filament has a
circular cross-section.
4. The stent of claim 1, further comprising a plurality of
filaments extending longitudinally within the lumen, wherein each
filament of the plurality of filaments is spaced from an adjacent
filament of the plurality of filaments.
5. The stent of claim 4, wherein the plurality of filaments
includes at least ten filaments.
6. The stent of claim 1, wherein the outer member is formed from a
cobalt-chromium alloy.
7. The stent of claim 6, wherein the at least one filament is
formed from tantalum.
8. The stent of claim 1, wherein the intermediate member is formed
from a radiopaque material.
9. The stent of claim 1, further comprising a biologically or
pharmacologically active agent disposed in the lumen.
10. A stent comprising: a hollow wire formed into a stent pattern,
wherein the hollow wire includes: an outer member having an outer
surface and an inner surface; a lumen extending longitudinally
within the hollow wire; a plurality of openings, wherein each
opening is disposed through the outer member to the lumen and
wherein each opening of the plurality of openings is spaced from
adjacent openings of the plurality of openings; and a plurality of
filaments extending longitudinally within the lumen, wherein each
filament of the plurality of filaments is spaced from adjacent
filaments of the plurality of filaments, and wherein no material is
disposed within spacing between adjacent filaments and spacing
between adjacent filaments of the plurality of filaments is
configured to permit tissue in-growth between the adjacent
filaments.
11. The stent of claim 10, wherein each filament of the plurality
of filaments extends a full length of the hollow wire.
12. The stent of claim 10, wherein each filament of the plurality
of filaments has a circular cross section.
13. A stent comprising: a hollow wire formed into a stent pattern,
wherein the hollow wire includes: an outer member having an outer
surface and an inner surface; a lumen extending longitudinally
within the hollow wire; at least one opening disposed through the
outer member to the lumen; and a plurality of filaments extending
longitudinally within the lumen, wherein each filament of the
plurality of filaments is spaced from adjacent filaments of the
plurality of filaments, and wherein the plurality of filaments
includes at least ten filaments, and wherein spacing between
adjacent filaments of the plurality of filaments is configured to
permit tissue in-growth between the adjacent filaments.
14. The stent of claim 13, wherein each filament of the plurality
of filaments extends a full length of the hollow wire.
15. The stent of claim 13, wherein each filament of the plurality
of filaments has a circular cross section.
16. The stent of claim 13, wherein the lumen is defined by the
inner surface of the outer member and extends longitudinally within
the outer member.
17. The stent of claim 13, wherein the stent further comprises: an
intermediate member lining at least a portion of the inner surface
of the outer member, the intermediate member having an outer
surface and an inner surface, and wherein the lumen is defined by
the inner surface of the intermediate member and extends
longitudinally within the intermediate member, and wherein the at
least one opening is disposed through the outer member and the
intermediate member to the lumen.
18. The stent of claim 13, further comprising a biologically or
pharmacologically active agent disposed in the lumen between
adjacent filaments of the plurality of filaments.
19. A stent comprising: a hollow wire formed into a stent pattern,
wherein the hollow wire includes: an outer member having an outer
surface and an inner surface; a lumen extending longitudinally
within the hollow wire, wherein the lumen is defined by the inner
surface of the outer member and extends longitudinally within the
outer member; at least one opening disposed through the outer
member to the lumen; and a plurality of filaments extending
longitudinally within the lumen, wherein each filament of the
plurality of filaments is spaced from adjacent filaments of the
plurality of filaments, and wherein no material is disposed within
spacing between adjacent filaments and the spacing between adjacent
filaments of the plurality of filaments is configured to permit
tissue in-growth between the adjacent filaments.
Description
FIELD OF THE INVENTION
The present invention relates to drug-filled stents and methods of
manufacturing drug-filled stents. More particularly, the present
invention relates to drug-filled stents with an increased lumen
surface area to promote tissue in-growth and methods of manufacture
thereof.
BACKGROUND OF THE INVENTION
Drug-eluting implantable medical devices, such as stents, have
become popular for their ability to perform their primary function,
i.e., providing structural support to a body vessel, and their
ability to medically treat the area in which they are
implanted.
For example, drug-eluting stents have been used to prevent
restenosis in coronary arteries. Drug-eluting stents may administer
active agents (also referred to herein as drugs) such as
anti-inflammatory compounds that block local invasion/activation of
monocytes, thus preventing the secretion of growth factors that may
trigger vascular smooth muscle cell (VSMC) proliferation and
migration. Other potentially anti-restenotic compounds include
antiproliferative agents, such as chemotherapeutics, which include
rapamycin and paclitaxel. Other classes of drugs such as
anti-thrombotics, anti-oxidants, platelet aggregation inhibitors
and cytostatic agents have also been suggested for anti-restenotic
use.
Drug-eluting implantable medical devices may be coated with a
polymeric material which, in turn, is impregnated with an active
agent or a combination of active agents. Once the medical device is
implanted at a target location, the active agent(s) is released
from the polymer for treatment of the local tissues. The active
agent(s) is released by a process of diffusion through the polymer
layer for biostable polymers, and/or as the polymer material
degrades for biodegradable polymers.
Controlling the rate of elution of a drug from the drug impregnated
polymeric material is generally based on the properties of the
polymer material. However, at the conclusion of the elution
process, the remaining polymer material in some instances has been
linked to an adverse reaction with the vessel, possibly causing
inflammation or a small but dangerous clot to form. Further, drug
impregnated polymer coatings on exposed surfaces of medical devices
may flake off or otherwise be damaged during delivery, thereby
preventing the drug from reaching the target site. Still further,
drug impregnated polymer coatings are limited in the quantity of
the drug to be delivered by the amount of a drug that the polymer
coating can carry and the size of the medical devices. Controlling
the rate of elution using polymer coatings is also difficult.
Stents with hollow, drug-filled structural members have been
contemplated and developed. For example, U.S. Pat. No. 6,071,305 to
Brown et al., generally discloses a stent formed of an elongated
member in a spiral tube configuration. The elongated member
includes a groove that can be filled with an active agent. Further,
U.S. Pat. No. 9,283,305 to Birdsall et al., U.S. Application
Publication No. 2011/0070358 to Mauch et al., U.S. Pat. No.
8,460,745 to Mitchell et al., and U.S. Pat. No. 9,119,736 to
Thompson, each of which is herein incorporated by reference in its
entirety, describe methods of forming and filling stents with
hollow, drug-filled structural members from composite wires. There
remains a need in the art for improvements of drug-filled
stents.
BRIEF SUMMARY OF THE INVENTION
Embodiments hereof relate to a stent including a hollow wire formed
into a stent pattern. The hollow wire includes an outer member, a
lumen, at least one opening, and at least one filament. The outer
member has an outer surface and an inner surface. The lumen extends
longitudinally within the hollow wire. The at least one opening
extends from the outer surface of the outer member to the lumen.
The at least one filament extends longitudinally within the lumen.
The at least one filament increases the amount of surface area
available for tissue in-growth within the lumen.
Embodiments hereof also relate to a stent including a hollow wire
formed into a stent pattern. The hollow wire includes an outer
member, a lumen, at least one opening, and a plurality of
filaments. The outer member has an outer surface and an inner
surface. The lumen extends longitudinally within the hollow wire.
The at least one opening extends from the outer surface of the
outer member to the lumen. The plurality of filaments extends
longitudinally within the lumen. Each filament of the plurality of
filaments is spaced from adjacent filaments of the plurality of
filaments, and the spacing between adjacent filaments of the
plurality of filaments is configured to permit tissue in-growth
between the adjacent filaments.
Embodiments hereof further relate to a method of forming a stent. A
composite wire including an outer member, a core member, and at
least one filament disposed within the core member is shaped into a
stent pattern. Openings are provided through the outer member to
the core member. The composite wire is processed to remove the core
member without adversely affecting the outer member or the at least
one filament.
BRIEF DESCRIPTION OF DRAWINGS
The foregoing and other features and advantages of the invention
will be apparent from the following description of embodiments
hereof as illustrated in the accompanying drawings. The
accompanying drawings, which are incorporated herein and form a
part of the specification, further serve to explain the principles
of the invention and to enable a person skilled in the pertinent
art to make and use the invention. The drawings are not to
scale.
FIG. 1 is a schematic illustration of a stent in accordance with an
embodiment hereof, wherein the stent is formed from a hollow wire
with a plurality of filaments and an active agent disposed within
the lumen of the hollow wire, the plurality of filaments forming an
increased surface area within the lumen of the hollow wire.
FIG. 2 is a cross-sectional view taken along line 2-2 of FIG.
1.
FIG. 3A is also a cross-sectional view of the hollow wire of FIG.
1, wherein the plurality of filaments and the active agent have
been omitted to illustrate a surface area within a lumen without
the plurality of filaments.
FIG. 3B is a cross-sectional view of the hollow wire of FIG. 1,
wherein the plurality of filaments is shown to illustrate the
increased surface area within the lumen with the plurality of
filaments and to illustrate the tissue growth interspersed between
the plurality of filaments after the active agent has eluted in
situ.
FIG. 4 is flow chart illustrating an embodiment of a method of
forming the stent of FIG. 1.
FIG. 5 is a schematic illustration of a composite wire which may be
utilized for forming a stent in the method of FIG. 4, the composite
wire including an outer member, a core member, and a plurality of
filaments.
FIG. 6 is a cross-sectional view of the composite wire of FIG. 5 at
a step in the method of FIG. 4, wherein the plurality of openings
has not been provided and the core member has not been processed
for removal.
FIG. 7 is a cross-sectional view of the composite wire of FIG. 5 at
a step in the method of FIG. 4, wherein the plurality of openings
has been provided but the core member has not been processed for
removal.
FIG. 8 is a cross-sectional view of the composite wire of FIG. 5 at
a step in the method of FIG. 4, wherein the plurality of openings
has been provided and the core member has been removed.
FIG. 9 is a cross-sectional illustration of a stent in accordance
with another embodiment hereof, wherein the stent is formed from a
hollow wire with a plurality of filaments and an active agent
disposed within the lumen of the hollow wire, the plurality of
filaments forming an increased surface area within the lumen of the
hollow wire, and wherein the stent is formed from a tri-layer
composite wire.
DETAILED DESCRIPTION OF THE INVENTION
Specific embodiments of the present invention are now described
with reference to the figures, wherein like reference numbers
indicate identical or functionally similar elements.
The following detailed description is merely exemplary in nature
and is not intended to limit the invention or the application and
uses of the invention. Although the description of embodiments
hereof is in the context of drug-filled medical devices for
delivering active agents within a body vessel, medical devices
described herein can also be used in other parts of the body.
Furthermore, the medical devices may not include active agents.
Additionally, there is no intention to be bound by any expressed or
implied theory presented in the preceding technical field,
background, brief summary or the following detailed
description.
A stent 100 in accordance with an embodiment hereof is described
herein and shown in FIGS. 1-2. The stent 100 is formed from a
hollow wire 102. The hollow wire 102 includes an outer member 104,
a lumen 106 defined by an inner surface 118 of the outer member 104
and extending longitudinally within the outer member 104. The
hollow wire 102 further includes a plurality of openings 122
extending through the outer member 104 to the lumen 106, and a
plurality of filaments 108 extending longitudinally within the
lumen 106. The term "wire" as used herein means an elongated
element or filament or group of elongated elements or filaments and
is not limited to a particular cross-sectional shape or material,
unless so specified.
In the embodiment of FIG. 1, the hollow wire 102 is formed into a
series of generally sinusoidal waveforms including generally
straight segments or struts 110 joined by bent segments or crowns
112. The waveform is helically wound to form the stent 100 into a
generally tubular configuration. In the embodiment shown in FIG. 1,
selected crowns 112 of longitudinally adjacent sinusoids may be
joined by, for example, fusion points 114. However, the invention
is not limited to the pattern or configuration shown in FIG. 1. The
hollow wire 102 of the stent 100 can be formed into any pattern
suitable for use as a stent. For example, and not by way of
limitation, the hollow wire 102 of the stent 100 can be formed into
patterns disclosed in U.S. Pat. No. 4,800,882 to Gianturco, U.S.
Pat. No. 4,886,062 to Wiktor, U.S. Pat. No. 5,133,732 to Wiktor,
U.S. Pat. No. 5,782,903 to Wiktor, U.S. Pat. No. 6,136,023 to
Boyle, and U.S. Pat. No. 5,019,090 to Pinchuk, each of which is
herein incorporated by reference in its entirety. Further, instead
of a single length of hollow wire formed into a stent pattern, a
plurality of hollow wires may be formed into a waveform and wrapped
into individual annular elements. The annular elements may then be
aligned along a common longitudinal axis and joined together to
form a stent having a generally tubular configuration.
As described above and best shown in FIG. 2, the hollow wire 102
includes the outer member 104. The outer member 104 includes an
outer surface 116 and the inner surface 118. In the embodiment of
FIG. 2, the lumen 106 is defined or formed from the hollow portion
of the outer member 104. The plurality of filaments 108 are
disposed within the lumen 106 and extend longitudinally through one
or more segments, sections or portions or for the full or entire
length of the hollow wire 102. The plurality of filaments 108 are
configured to increase the surface area within the lumen 106 for
improved tissue in-growth as described in more detail below. The
plurality of filaments 108 each have an outer surface 120. In the
embodiment of FIG. 2, each filament 108 is generally spaced apart
from each adjacent filament 108. In other words, each filament 108
is adjacent to, but not substantially in contact with any other
filament 108. The spacing between adjacent filaments 108 is
configured to permit and encourage tissue in-growth there-between.
In addition, each filament 108 is also substantially spaced apart
from the inner surface 118 of the outer member 104 so as to be
adjacent to, but not in contact with the inner surface 118 of the
outer member 104. The spacing may be selected to elicit a specific
desired cell behavior or behavior set. While the hollow wire 102 is
shown with eighteen (18) filaments 108, this is by way of example
and not limitation, and the hollow wire 102 may include more or
fewer filaments 108. Additionally, while each filament 108 is shown
as having a generally circular cross-section, each filament 108 may
have cross-sections of different shapes and/or sizes. The
combination of one or more different shapes and/or sizes along one
or more segments of each of the filaments 108 and/or between each
of the filaments 108 may be selected to encourage preferred tissue
in-growth of one or more cell types having one or more desired cell
behaviors at one or more select locations of the stent 100.
Further, although the hollow wire 102 is shown as generally having
a circular cross-section along the entire length of the hollow wire
102, the hollow wire 102 may be generally elliptical or rectangular
in cross-section. In some embodiments, the cross-sectional shape
and/or size can vary along one or more segments of the hollow wire
102.
Although the plurality of filaments 108 have been described herein
as extending the entire or full length of the hollow wire 102, this
is by way of example and not limitation. It will be understood that
the plurality of filaments 108, and more precisely each filament
108 of the plurality of filaments 108 may extend a distance or
length less than the entire or full length of the hollow wire 102.
Additionally, each filament 108 may start and stop along the length
of the hollow wire 102 to form segments along the length of the
hollow wire 102. Further, the segments of the plurality of
filaments 108 may be positioned at select portions or locations of
the stent 100 such as one or more crowns 112, one or more struts
110, or any combination thereof. In another embodiment, the
segments of the plurality of filaments 108 may be positioned at the
end portions of the stent 100. Positioning of the segments of the
plurality of filaments 108 at select locations of the stent 100 may
be utilized to encourage preferred tissue in-growth having one or
more desired cell behaviors in select locations. The positioning of
the segments of the plurality of filaments 108 at select locations
of the stent 100 in combination with the selection of one or more
shapes and/or sizes along one or more segments of each of the
filaments 108 can be selected to create the desired amount of space
between adjacent filaments 108 to selectively encourage preferred
tissue in-growth of one or more cell types having one or more
desired cell behaviors at one or more select locations of the stent
100.
FIGS. 3A and 3B illustrate the stent 100 without and with the
plurality of filaments 108, respectively, and are included herein
to illustrate the increase in the surface area within the lumen 106
with the plurality of filaments 108. Referring to FIG. 3A, when the
plurality of filaments 108 are not present, the surface area
available for tissue in-growth within the lumen 106 is only the
inner surface 118 of the outer member 104. Stated another way,
tissue TG may attach to the stent 100 within the lumen 106 only
along the inner surface 118 of the outer member 104. However, as
shown in FIG. 3B, when the plurality of filaments 108 are present,
the surface area available for tissue in-growth within the lumen
106 includes both the inner surface 118 of the outer member 104 and
the outer surface 120 of each filament 108. Thus, tissue TG may
attach to the stent 100 within the lumen 106 along both the inner
surface 118 of the outer member 104 and the outer surface 120 of
each filament 108. Accordingly, the plurality of filaments 108
increases the surface area available for tissue in-growth within
the lumen 106 of the stent 100 as will be described in more detail
herein.
In the embodiment of FIG. 2, a biologically or pharmacologically
active agent 150 (hereafter referred to as "active agent 150" for
simplicity) is deposited within the lumen 106 and around the
plurality of filaments 108 of the hollow wire 102. In the
embodiment of FIG. 2, the plurality of openings 122 provide access
to the lumen 106 to permit the active agent 150 to be released from
the lumen 106. Further, the plurality of openings 122 provide
access to the lumen 106 to permit tissue in-growth into the lumen
106 after the active agent 150 has been released from the lumen
106. The plurality of openings 122 may be sized and shaped as
desired to control both the elution rate of the active agent 150
from the lumen 106 and to control the in-growth of cells into the
lumen 106 of the stent 100. Larger sized openings 122 generally
permit a faster elution rate and a faster in-growth rate and
smaller sized openings 122 generally provide a slower elution rate
and a slower in-growth rate. The size and/or quantity of the
plurality of openings 122 may be varied along the stent 100 in
order to vary both the quantity and/or rate of the active agent 150
being eluted from stent 100 and the in-growth of cells into the
lumen 106 at different portions of stent 100. The plurality of
openings 122 may be, for example and not by way of limitation,
10-40 .mu.m in diameter. While shown in FIG. 1 with the plurality
of openings 122 on an outwardly facing or abluminal surface 124,
this is by way of example and not limitation, and the plurality of
openings 122 may be provided on the abluminal surface 124 and/or on
an inward facing or luminal surface 125, or may be provided
anywhere along the circumference of the hollow wire 102.
As used herein, a biologically or pharmacologically "active agent"
may include, but is not limited to, antineoplastic, antimitotic,
anti-inflammatory, antiplatelet, anticoagulant, antifibrin,
antithrombin, antiproliferative, antibiotic, antioxidant, and
antiallergic substances as well as combinations thereof. Examples
of such antineoplastics and/or antimitotics include paclitaxel
(e.g., TAXOL.RTM. by Bristol-Myers Squibb Co., Stamford, Conn.),
docetaxel (e.g., Taxotere.RTM. from Aventis S. A., Frankfurt,
Germany), methotrexate, azathioprine, vincristine, vinblastine,
fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin.RTM. from
Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g.,
Mutamycin.RTM. from Bristol-Myers Squibb Co., Stamford, Conn.).
Examples of such antiplatelets, anticoagulants, antifibrin, and
antithrombins include sodium heparin, low molecular weight
heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost,
prostacyclin and prostacyclin analogues, dextran,
D-phe-pro-arg-chloromethylketone (synthetic antithrombin),
dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor
antagonist antibody, recombinant hirudin, and thrombin inhibitors
such as Angiomax.TM. (Biogen, Inc., Cambridge, Mass.). Examples of
such cytostatic or antiproliferative agents include ABT-578 (a
synthetic analog of rapamycin), rapamycin (sirolimus), zotarolimus,
everolimus, angiopeptin, angiotensin converting enzyme inhibitors
such as captopril (e.g., Capoten.RTM. and Capozide.RTM. from
Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or
lisinopril (e.g., Prinivil.RTM. and Prinzide.RTM. from Merck &
Co., Inc., Whitehouse Station, N.J.), calcium channel blockers
(such as nifedipine), colchicine, fibroblast growth factor (FGF)
antagonists, fish oil (omega 3-fatty acid), histamine antagonists,
lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol
lowering drug, brand name Mevacor.RTM. from Merck & Co., Inc.,
Whitehouse Station, N.J.), monoclonal antibodies (such as those
specific for Platelet-Derived Growth Factor (PDGF) receptors),
nitroprusside, phosphodiesterase inhibitors, prostaglandin
inhibitors, suramin, serotonin blockers, steroids, thioprotease
inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric
oxide. An example of an antiallergic agent is permirolast
potassium. Other active substances or agents that may be used
include nitric oxide, alpha-interferon, genetically engineered
epithelial cells, and dexamethasone. In other examples, the active
substance is a radioactive isotope for implantable device usage in
radioactive procedures. Examples of radioactive isotopes include,
but are not limited to, phosphorus (P.sup.32), palladium
(Pd.sup.103), cesium (Cs.sup.131), Iridium (I.sup.192) and iodine
(I.sup.125). While the preventative and treatment properties of the
foregoing active substances or agents are well-known to those of
ordinary skill in the art, the substances or agents are provided by
way of example and are not meant to be limiting. Other active
substances are equally applicable for use with the disclosed
methods and compositions. Further, a carrier may be used with the
biologically or pharmacologically active agent. Examples of
suitable carriers include, but are not limited to, ethanol,
acetone, tetrahydrofuran, dymethylsulfoxide, a combination thereof,
or other suitable carriers known to those skilled in the art. Still
further, a surfactant may be formulated with the drug and the
solvent to aid elution of the drug.
While described herein with the active agent 150 within the lumen
106, this is not meant to be limiting, and in an alternative
embodiment, the lumen 106 may not contain the active agent 150.
When the active agent 150 is not utilized, the plurality of
openings 122 provide access to the lumen 106 only to permit tissue
in-growth into the lumen 106. Accordingly, in such an embodiment,
the plurality of openings 122 are sized and shaped to control only
the in-growth of cells into the lumen 106 of the stent 100.
The ends 126 of the hollow wire 102 may be closed by crimping
excess material of the hollow wire 102 to close the lumen 106. The
ends 126 may also be closed by not removing a core member during
the method of manufacture thereof, described in more detail below,
from the ends 126. In the embodiment of FIG. 2, with the active
agent 150 disposed within the lumen 106, closing the ends 126
prevents the active agent 150 from prematurely releasing from the
ends 126. However, closing the ends 126 is not required as the
active agent 150 may be dried, provided within a polymer matrix,
enclosed within a liner (not shown in FIGS. 1-2), or otherwise
protected from premature release from the ends 126. Further, the
ends 126 may be welded, crimped or otherwise connected to other
portions of the hollow wire 102 such that the ends 126 are not free
ends.
When the stent 100 is deployed within a vessel, the active agent
150 elutes from the lumen 106 of the stent 100. Once the active
agent 150 has been eluted, cells originating from the vessel
migrate through the plurality of openings 122 and into the lumen
106. The cells attach or couple to the surfaces within the lumen
106. More specifically, the cells grow or fill the spaces between
adjacent filaments 108 and couple to the inner surface 118 of the
outer member 104 and to the outer surface 120 of each filament 108
as shown in FIG. 3B described above. Once attached thereto, the
cells grow or colonize and form an extracellular matrix within the
lumen 106 of the stent 100 to couple the stent 100 to the vessel.
The spaces between the plurality of filaments 108 are all in fluid
communication with each other in order to permit tissue in-growth
between and around each individual filament 108. The increased
surface area available within the lumen 106 with the plurality of
filaments 108 permits more cells to couple to the stent 100, and
thus more firmly anchors the stent 100 to the vessel. The improved
mechanical integration, or coupling of the stent 100 to the vessel
may offer clinical benefit in reducing micro-damage to the tissue
surrounding the stent 100 during biomechanical motion of the
vessel, such as the repetitive constriction and dilation of the
vessel due to cardiac pressure differentials of the cardiac cycle.
The term "micro-damage," as used herein, means tissue damage due to
the relative movement between a generally rigid stent and a
generally flexible vessel. Further, the term "biomechanical
motion," as used herein means the motion or movement of a vessel.
For example, and not by way of limitation, biomechanical motion
includes the repetitive constriction and dilation of a body vessel
due to cardiac pressure differentials of the cardiac cycle.
In embodiments without the active agent 150, when the stent 100 is
deployed within a vessel, the cells of the vessel adjacent the
plurality of openings 122 migrate through the plurality of openings
122 and into the lumen 106 to couple the stent 100 to the vessel as
previously described.
FIGS. 4-8 show a method for forming a stent from a hollow wire,
such as the stent 100, in accordance with an embodiment hereof. As
shown in FIG. 4, step 201 is to utilize a composite wire 130 having
the outer member 104, the plurality of filaments 108, and a core
member 128, shown schematically in FIG. 5 and in cross-section in
FIG. 6. The outer member 104 and the plurality of filaments 108
form the hollow wire 102 of the stent 100 described above with
respect to FIGS. 1-2 after processing thereof to form the stent
100. The composite wire 130 may be formed by any method known in
the art, for example and not by way of limitation, a co-drawing
process, extrusion, cladding, or any other suitable method. Stated
another way, the composite wire 130 may be formed by methods of
forming composite wires known to those skilled in the art. Examples
of composite wires and methods of forming composite wires can be
found in U.S. Pat. No. 5,630,840 to Mayer, U.S. Pat. No. 6,248,190
to Stinson, U.S. Pat. No. 6,497,709 to Heath, and U.S. Pat. No.
7,101,392 to Heath, each of which is herein incorporated by
reference in its entirety.
The outer member 104 may be any material that is suitable to be
used as a stent. More particularly, the requirements for the
material of the outer member 104 are that it be biocompatible,
sufficiently resilient to be used as a stent, and that it survives
the process for eliminating the core member 128, as described in
more detail below. For example, and not by way of limitation, the
outer member 122 may be a cobalt-chromium alloy. As used herein,
the term "cobalt-chromium" alloy includes alloys with cobalt and
chromium. Generally, materials such as, but not limited to,
cobalt-nickel-chromium alloys ("MP35N" and "MP20N") and
chromium-nickel-tungsten-cobalt alloys ("L605") and
cobalt-chromium-nickel-molybdenum alloys ("ELGILOY") are the types
of materials included in the term "cobalt-chromium alloys" as used
herein.
Similarly, the plurality of filaments 108 may be any material that
it is biocompatible, is sufficiently resilient to be used as a
stent, and that survives the process for eliminating the core
member 128. In an embodiment hereof, the plurality of filaments 108
may be a radiopaque material to permit the stent 100 to be visible
under X-ray or fluoroscopic imaging equipment when the outer member
104 is made of a material that is difficult to visualize under
X-ray or fluoroscopic imaging equipment. Thus, selection of the
plurality of filaments 108 depends on the material of the core
member 128, the process selected for removing the core member 128,
and the desired radiopacity of the plurality of filaments 108.
The core member 128 is a sacrificial material that is removed
without damaging the plurality of filaments 108 or the outer member
104. In the embodiment of FIGS. 4-8, the core member 128 includes a
plurality of longitudinal bores 138, as shown in FIG. 5. Each bore
138 may be formed by methods such as, but not limited to mechanical
laser cutting, drilling, etching, or any other suitable method. A
single filament 108 is disposed within each bore 138. The inner
diameter of each bore 138 is slightly greater than the outer
diameter of each filament 108. The term "slightly greater," as used
herein means that the inner surface of each bore 138 has a larger
cross-section than the cross-section of the corresponding filament
108 such that the corresponding filament 108 may slide or be
disposed within the bore 138. The placement of the longitudinal
bores 138 through the core member 128 determines the spacing
between or pattern of the plurality of filaments 108 within hollow
wire 102, which in turn dictates the amount of tissue in-growth and
specific desired cell behavior as previously described in more
detail above. Stated another way, the core member 128 and the
longitudinal bores 138 essentially form a template that dictates
the placement of the plurality filaments 108 within the lumen 106
of the hollow wire 102. After the plurality of filaments 108 are
disposed within the core member 128, the core member 128 and the
plurality of filaments 108 are collectively disposed within the
outer member 104. The outer member 104, the core member 128 and the
plurality of filaments 108 then undergo a process such as a
co-drawing process to form the composite wire 130, as shown in FIG.
6.
In a non-limiting example, the outer member 104 is made of MP35N,
the plurality of filaments 108 is made of tantalum, and the core
member 128 is made of silver. In the non-limiting example, the
process to remove the core member 128 is exposing the core member
128 to nitric acid. Other examples of material combinations of the
outer member 104, the plurality of filaments 108, the core member
128, and the removal method are provided below in chart form.
While described herein with a boring and co-drawing process, this
is by way of example and not limitation. In another embodiment, the
composite wire 130 with the plurality of filaments 108 may be
formed in a combination process such as the process utilized for
manufacturing superconducting filaments. Examples of composite
filaments and methods of forming composite filaments can be found
in U.S. Pat. No. 5,630,840 to Mayer, U.S. Pat. No. 6,248,190 to
Stinson, U.S. Pat. No. 6,497,709 to Heath, and U.S. Pat. No.
7,101,392 to Heath, each of which has been previously incorporated
by reference herein.
Referring back to FIG. 4, step 211 is to shape the composite wire
130 into the stent pattern. As discussed above, the stent pattern
can be the pattern shown in FIG. 1 or any other suitable pattern
formed from a wire. Further, although the order of all the steps is
not critical, step 211 should be performed prior to removing the
core member 128, as explained below. The step of shaping the
composite member 130 into the stent pattern does not have to
include shaping the composite member 130 into the final stent
pattern. For example, the step 211 of shaping the composite member
130 into a stent pattern may include only forming the struts 110
and the crowns 112 with the composite wire 130. Shaping the
composite wire 130 into the stent pattern while the core member 128
is disposed within the outer member 104 helps prevent kinking or
other deformations from occurring in the outer member 104. Shaping
the composite wire 130 into the stent pattern shown in FIG. 1
generally includes the steps of forming the composite wire 130 into
a waveform pattern followed by wrapping the waveform pattern around
a mandrel, as known to those skilled in the art. The end result is
a helical stent pattern formed onto a mandrel. Selected crowns 112
of the waveform pattern may then be fused together and the stent
may be removed from the mandrel. In addition to the technique
described above, step 211 of shaping the composite wire 130 into
the stent pattern can be performed with techniques known to those
skilled in the art. For example, and not by way of limitation,
forming the composite wire 130 into a waveform can be achieved
using techniques described in U.S. Application Publication No.
2010/0269950 to Hoff et al. and U.S. Pat. No. 9,296,034 to Costa et
al., each of which is herein incorporated by reference in its
entirety, and U.S. Application Publication No. 2011/0070358 to
Mauch et al., previously incorporated by reference. Other
techniques understood by persons skilled in the art could also be
used.
Step 221, shown in FIG. 4 as well as FIG. 7, is to provide the
plurality of openings 122 through the outer member 104. The
plurality of openings 122 may be laser cut, drilled, etched, or
otherwise provided through the outer member 104. Step 221 is not
required to be performed after step 211 or before step 231.
However, it is preferred for step 221 to be performed before step
231 as the plurality of openings may be utilized as access to the
core member 128 for processing, as explained in more detail below.
If step 221 is performed after step 211, a cross-section of the
composite wire 130 will include the outer member 104, the plurality
of filaments 108, the core member 128, and one or more opening(s)
122 as shown in FIG. 7.
Step 231 is to remove the core member 128 from the lumen 106 of the
outer member 104 without adversely affecting the outer member 104
or the plurality of filaments 108, such as by chemical etching.
Step 231 can be performed by any suitable process for removing the
core member 128 while preserving the outer member 104 and the
plurality of filaments 108. In particular, exposing the composite
wire 130 formed from an outer member 104 of MP35N, a plurality of
filaments 108 of tantalum (Ta), and a core member 128 of silver
(Ag) to nitric acid (NaNO3) causes the nitric acid (NaNO3) to react
with the silver (Ag) core member 128 to form nitrogen monoxide
(NO), silver nitrate (AgNO3), and water (H2O), which can be removed
from the lumen 106. Nitric acid (NaNO3) reacts similarly with a
core member 128 made from copper (Cu). However, nitric acid (NaNO3)
does not react with an outer member 104 formed of MP35N or the
plurality of filaments 108 formed of tantalum (Ta) described above.
Accordingly, after step 231 is completed, the outer member 104 and
the plurality of filaments 108 remain, and the core member 128 has
been removed, leaving the cross-sectional structure shown in FIG.
8. As noted above, the plurality of openings 122 do not need to be
formed prior to the step of removing the core member 128 as long as
there is a way to expose the core member 128 to the etchant. For
example, the ends 126 of the wire may be open or temporary ports
may for formed through the outer member 104 to expose the core
member 128 to the etchant.
Although a particular embodiment of the outer member 104 made from
MP35N, the plurality of filaments 108 made from tantalum, the core
member 128 made from silver, and a nitric acid etchant has been
described, those skilled in the art would recognize that other
combinations of materials and etchants could be utilized. For
example, and not by way of limitation, the combination of materials
and etchants described in the chart below may be utilized. Further,
other materials and methods for removing core members may be used,
as described, for example, in U.S. Application Publication No.
2011/0008405 to Birdsall et al. and U.S. Application Publication
No. 2011/0070358 to Mauch et al., each of which has been previously
incorporated by reference.
TABLE-US-00001 Outer Intermediate Etchant Member Member Core Member
Xenon- Cobalt-chromium Pt20Ir, Tantalum, tungsten, difluoride
alloys (MP35N, Pt10Ir molybdenum, MP20N, L605, niobium, ELGILOY)
rhenium, carbon, germanium, silicon, Ta--2.5W Nitric
Cobalt-chromium Tantalum, Copper Acid, alloys (MP35N, Ta--2.5W
sulfuric MP20N, L605, acid ELGILOY) Nitinol, Titanium, Titanium
alloys Nitric Cobalt-chromium Tantalum, Silver Acid alloys (MP35N,
Ta--2.5W MP20N, L605, ELGILOY) Nitinol, Titanium, Titanium alloys
Water, Cobalt-chromium Pt20Ir, Zinc, salt water alloys (MP35N,
Pt10Ir, Magnesium MP20N, L605, Tantalum, ELGILOY), Ta--2.5W
stainless steel, Nitinol, Titanium, Titanium alloys Heat
Cobalt-chromium Pt20Ir, Zinc, (separation alloys (MP35N, Pt10Ir,
Magnesium via melt or MP20N, L605, Tantalum, sublimation) ELGILOY),
Ta--2.5W stainless steel, Nitinol, Titanium, Titanium alloys Xenon
Cobalt-chromium Pt20Ir, Titanium, difluoride alloys (MP35N, Pt10Ir
Titanium Dilute HF MP20N, L605, alloys ELGILOY
Step 241 is to fill the lumen 106 of the outer member 104 with the
active agent 150. The lumen 106 may be filled by methods known to
those skilled in the art. Examples of methods of filling a drug
eluting device can be found in U.S. Pat. No. 8,460,745 to Mitchell
et al., U.S. Pat. No. 8,381,774 to Mitchell et al., U.S. Pat. No.
8,678,046 to Mitchell et al., U.S. Pat. No. 8,632,846 to Avelar et
al., U.S. Pat. No. 8,828,474 to Avelar et al., U.S. Pat. No.
9,549,832 to Peterson et al., and U.S. Pat. No. 9,204,982 to
Peterson et al., each of which is herein incorporated by reference
in its entirety. In embodiments without the active agent 150, step
241 is omitted. In an embodiment, the spacing between the filaments
108 prior to disposing an active agent there between, or in the
absence of an active agent prior to the ingrowth of tissue, may be
maintained by one or more of the methods described below. More
particularly, in an embodiment, the spacing between the filaments
108 may be maintained by securing the filaments 108 at the ends 126
of the hollow wire 102. In another embodiment, spacers (not shown)
may be disposed at desired increments along the length of the
hollow wire 102 during the initial wire draw to maintain spacing
between the filaments 108. In yet another embodiment, the core
member 128 may be only partially removed such that portions of the
core member 128 remain at desired locations, such as but not
limited to the crowns 112 of the hollow wire 102, to maintain the
spacing of the filaments 108. However, since tissue-ingrowth may
displace the filaments, it is not required to utilize one of the
above-described methods for maintaining spacing between the
filaments 108.
Although the stent 100 has been described herein as formed from a
bi-layer composite wire with an outer member and a core member,
this is not meant to be limiting, and it will be understood that in
an alternate embodiment, a stent 100' may be formed from a
tri-layer composite wire. As shown in FIG. 9, which is a
cross-sectional view of the stent 100' formed of a tri-layer
composite wire after processing to remove a core member, the
tri-layer composite wire embodiment of the stent 100' generally
includes an outer member 104', an intermediate member 140 lining at
least a portion of the outer member 104', and the core member (not
shown in FIG. 9, as the core member would be removed during
processing as described above with respect to FIG. 4). The
intermediate member 140 includes an inner surface 142 and an outer
surface 144. In this embodiment, a lumen 106' is defined by the
inner surface 142 of the intermediate member 140 and at least one
opening 122' is disposed through the outer member 104' and the
intermediate member 140 to the lumen 106'. The intermediate member
140 may be formed of a radiopaque material to permit the stent 100'
to be visible under X-ray or fluoroscopic imaging equipment when
the outer member is made of a material that is difficult to
visualize under X-ray or fluoroscopic imaging equipment.
While various embodiments according to the present invention have
been described above, it should be understood that they have been
presented by way of illustration and example only, and not
limitation. Various changes in form and detail can be made therein
without departing from the spirit and scope of the invention. Thus,
the breadth and scope of the present invention should not be
limited by any of the above-described exemplary embodiments, but
should be defined only in accordance with the appended claims and
their equivalents. It will also be understood that each feature of
each embodiment discussed herein, and of each reference cited
herein, can be used in combination with the features of any other
embodiment. All patents and publications discussed herein are
incorporated by reference herein in their entirety.
* * * * *
References